The goal of this program is to understand cellular transformation at the molecular level: both the genetic events which induce transformation and the alteration in biochemical events which ensue. There are five component sections: Human Oncogenes (Wigler) focuses on new human oncogenes which have either a novel structure or an interesting pattern of expression in neoplasia. Oncogenesis in Transgenic Mice (Hanahan and Field) utilizes a relatively new technology to explore the multistep nature of carcinogenesis in specific tissues. c-fos Transcriptional Activation (Gilman) explores the molecules which induce fos oncogene expression in response to signal transduction. Tropomyosins and Transformation (Helfman) analyses changes in the expression of the tropomyosin isoforms and their effects on the transformed phenotype. Membrane Signal Transduction (Feramisco and Bar-Sagi) describes the interactions of various second messenger systems related to growth proliferation signals which originate at the cellular membrane. The project brings together five diverse approaches to a common problem.